TY  - JOUR
AU  - Michanski, Susann
AU  - Kapoor, Rohan
AU  - Steyer, Anna M
AU  - Möbius, Wiebke
AU  - Früholz, Iris
AU  - Ackermann, Frauke
AU  - Gültas, Mehmet
AU  - Garner, Craig C
AU  - Hamra, F Kent
AU  - Neef, Jakob
AU  - Strenzke, Nicola
AU  - Moser, Tobias
AU  - Wichmann, Carolin
TI  - Piccolino is required for ribbon architecture at cochlear inner hair cell synapses and for hearing.
JO  - EMBO reports
VL  - 24
IS  - 9
SN  - 1469-221X
CY  - Hoboken, NJ [u.a.]
PB  - Wiley
M1  - DZNE-2023-00888
SP  - e56702
PY  - 2023
AB  - Cochlear inner hair cells (IHCs) form specialized ribbon synapses with spiral ganglion neurons that tirelessly transmit sound information at high rates over long time periods with extreme temporal precision. This functional specialization is essential for sound encoding and is attributed to a distinct molecular machinery with unique players or splice variants compared to conventional neuronal synapses. Among these is the active zone (AZ) scaffold protein piccolo/aczonin, which is represented by its short splice variant piccolino at cochlear and retinal ribbon synapses. While the function of piccolo at synapses of the central nervous system has been intensively investigated, the role of piccolino at IHC synapses remains unclear. In this study, we characterize the structure and function of IHC synapses in piccolo gene-trap mutant rats (Pclogt/gt ). We find a mild hearing deficit with elevated thresholds and reduced amplitudes of auditory brainstem responses. Ca2+ channel distribution and ribbon morphology are altered in apical IHCs, while their presynaptic function seems to be unchanged. We conclude that piccolino contributes to the AZ organization in IHCs and is essential for normal hearing.
KW  - Rats
KW  - Animals
KW  - Hair Cells, Auditory, Inner
KW  - Hearing: physiology
KW  - Synapses: physiology
KW  - Cochlea
KW  - Spiral Ganglion: metabolism
KW  - Cytoskeletal Proteins: metabolism
KW  - Neuropeptides
KW  - Ca2+ channel (Other)
KW  - active zone (Other)
KW  - cochlea (Other)
KW  - hearing (Other)
KW  - synaptic vesicle (Other)
KW  - Pclo protein, rat (NLM Chemicals)
KW  - Cytoskeletal Proteins (NLM Chemicals)
KW  - Neuropeptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:37477166
C2  - pmc:PMC10481675
DO  - DOI:10.15252/embr.202256702
UR  - https://pub.dzne.de/record/263802
ER  -